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Impact of linkage disequilibrium on multipoint linkage analysis

Part 1. Genetics

1.4. Gene Mapping

Short Specialist Review

  1. Christopher I. Amos1,
  2. Qiqing Huang2

Published Online: 15 JUL 2006

DOI: 10.1002/047001153X.g104312

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

How to Cite

Amos, C. I. and Huang, Q. 2006. Impact of linkage disequilibrium on multipoint linkage analysis. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics.

Author Information

  1. 1

    U.T.M.D. Anderson Cancer Center, Houston, TX, US

  2. 2

    Johnson & Johson Pharmaceutical Research and Development, Raritan, NJ, US

Publication History

  1. Published Online: 15 JUL 2006

Abstract

In this chapter we describe the impact that an inaccurate assumption of linkage equilibrium has upon linkage methods. Most multipoint linkage analysis programs assume linkage equilibrium among tightly linked markers. Violation of this assumption leads to biased evidence for linkage when analyzing affected sib-pairs and an excess probability of falsely detecting evidence for linkage. Including the parents in the analysis or additional unaffected siblings reduces or eliminates this bias. Procedures for removing markers in strong linkage disequilibrium (LD) or for treating linked markers as sets of alleles at a single locus have been developed. Some parametric linkage methods can perform analysis incorporating haplotype frequencies among tightly linked markers, but these approaches are awkward to implement for dense multipoint mapping.

Keywords:

  • linkage;
  • linkage disequilibrium;
  • mapping;
  • LOD scores;
  • false positive;
  • bias